I. 有機鹼試劑控制多樣性導向串聯反應合成螺環環己烯1,3茚二酮衍生物以及香豆素稠合環戊烷衍生物 II. 透過手性輔助基控制分子內Wittig反應立體選擇性建構手性雜環-芳基阻旋異構物
No Thumbnail Available
Date
2020
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
第一部分:此論文第一部分研究為 3-高醯基香豆素與 β-芳基烯基-1,3-茚二酮衍生物進行化學選擇性連續反應之研究。其兩起始物經 1,6-加成反應後，因 dienolate 中間體具有高度活性，可藉由有機鹼試劑控制反應的位向選擇性進行 aldol 或 vinylogous Michael 反應，達成化學選擇性之多樣性導向連續反應的結果，並分別建構具有生物活性潛力之螺環環己烯-1,3-茚二酮以及香豆素稠合環戊烷衍生物。
第二部分:此論文第二部分主要承襲實驗室先前開發之磷兩性離子研究，經由喹諾酮與含有手性輔助基之萘醛衍生物以及三丁基磷試劑進行三組分反應合成手性磷兩性離子作為起始物。並使其與醯化試劑進行氧醯化及手性輔助基控制之手性分子內 Wittig 反應建構手性雜環-芳基阻旋異構物-呋喃喹諾酮阻旋異構物。其生成之手性非鏡像阻旋異構物可經由管柱層析法分離純化，再個別去除手性輔助基後可得兩高光學純度之雜環-芳基阻旋異構物。
Part I: An organobase-controlled, divergent cascade reaction to construct biological active framework spirocyclohexene indane-1, 3-diones and coumarin-fused cyclopentanes is reported in up to 85% yield and excellent diastereoselectivity. The cascade reaction was triggered by the 1,6-addition of 3- homoacylcoumarins to the indanedione-derived acceptors and further regio/chemoselective reactions that preferentially resulted in desired products, respectively. The mechanism shows that the 1, 6-addition/aldol and 1, 6-addition/vinylogous Michael addition cascade processes were controlled by a rational choice of the base/solvent systems to the predominant formation of one of the two carbocyclic compounds. Part II: In the second part, a series of the chiral phosphorus zwitterions were synthesized from the three-component reaction of 4-hydroxy-1-methyl-quinolone, chiral auxiliary-bonded 2-hydroxy-1-naphthaldehyde, and tributylphosphine. Chiral phosphorus zwitterions were further utilized to undergo O-acylation smoothly with various acid chlorides, providing axially chiral heterobiaryl atropisomers via intramolecular Wittig reaction. The resulting diastereomers of axially chiral heterobiaryl atropisomers could be separated successfully by column chromatography. Furthermore, the chiral auxiliary group of each diastereomer could be removed to obtain the corresponding enantiopure chiral heterobiaryl atropisomers up to 99% of enantiomeric excess.
Part I: An organobase-controlled, divergent cascade reaction to construct biological active framework spirocyclohexene indane-1, 3-diones and coumarin-fused cyclopentanes is reported in up to 85% yield and excellent diastereoselectivity. The cascade reaction was triggered by the 1,6-addition of 3- homoacylcoumarins to the indanedione-derived acceptors and further regio/chemoselective reactions that preferentially resulted in desired products, respectively. The mechanism shows that the 1, 6-addition/aldol and 1, 6-addition/vinylogous Michael addition cascade processes were controlled by a rational choice of the base/solvent systems to the predominant formation of one of the two carbocyclic compounds. Part II: In the second part, a series of the chiral phosphorus zwitterions were synthesized from the three-component reaction of 4-hydroxy-1-methyl-quinolone, chiral auxiliary-bonded 2-hydroxy-1-naphthaldehyde, and tributylphosphine. Chiral phosphorus zwitterions were further utilized to undergo O-acylation smoothly with various acid chlorides, providing axially chiral heterobiaryl atropisomers via intramolecular Wittig reaction. The resulting diastereomers of axially chiral heterobiaryl atropisomers could be separated successfully by column chromatography. Furthermore, the chiral auxiliary group of each diastereomer could be removed to obtain the corresponding enantiopure chiral heterobiaryl atropisomers up to 99% of enantiomeric excess.
Description
Keywords
多樣性導向合成, 1-6-加成, 羥醛反應, vinylogous麥克加成, 分子內 Wittig 反應, 手性輔助基, 雜環-芳基阻旋異構物, Diversity-Oriented synthesis, 1-6-addition, vinylogous Micheal addtion, Intramolecular Wittig Reaction, Chiral Auxiliary, Heterobiaryls Atropisomers